Treatment of animal models of Alzheimer’s disease with extracellular vesicles or exosomes and involvement of microRNAs

Abstract Alzheimer’s disease is a complex and devastating neurodegenerative disorder that accounts for roughly 80% of all dementia cases. It is primarily marked by the accumulation of senile amyloid-β plaques and neurofibrillary tangles composed of hyperphosphorylated tau protein. These pathological features are accompanied by chronic neuroinflammation and glial cell dysfunction, which collectively contribute to the progressive loss of synapses and neurons. As a result, individuals with Alzheimer’s disease experience gradual memory loss and cognitive decline. Currently, the global patient population is nearing 50 million, a number expected to increase dramatically over the coming decades. Conventional treatments focus on symptom management through acetylcholinesterase inhibitors, such as donepezil, galantamine, and rivastigmine, and the N-methyl-D-aspartate receptor antagonist memantine. However, the past few years have seen the approval of newer agents such as sodium oligomannate, aducanumab, and lecanemab, which show some promise in slowing disease progression. Unfortunately, most patients are not diagnosed until moderate or advanced stages when irreversible brain damage has occurred. This highlights an urgent need for early diagnosis and biomarkers together with therapeutic strategies aimed at early-stage intervention and identifying novel drug targets that address prodromal and established forms of the disease. This article is a literature review of extracellular vesicles/exosomes treatment in animal models of Alzheimer’s disease involving microRNAs. In the in vivo animal studies of Alzheimer’s disease reviewed, extracellular vesicles and exosomes from various sources improved memory and cognitive decline, lowered inflammation and amyloid deposition, and increased neuron survival in the brain. Loading extracellular vesicles and exosomes with microRNA mimics (e.g., miR-22, -29b, -124, -132, -138-5p, -342-5p, -711, and -7670-3p) or antagomirs (e.g., miR-206-antagomir) improved outcomes in animal models of Alzheimer’s disease. Supporting results were found in the in vitro cell studies reviewed.